18-41955310-T-G

Position:

chr18-41955310-T-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_002647.4(PIK3C3):c.19T>G(p.Phe7Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000868 in 1,613,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

PIK3C3
NM_002647.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.05

Variant links:

Genes affected

PIK3C3 (HGNC:8974): (phosphatidylinositol 3-kinase catalytic subunit type 3) Enables 1-phosphatidylinositol-3-kinase activity. Involved in early endosome to late endosome transport and regulation of cytokinesis. Acts upstream of or within autophagy and protein lipidation. Located in autolysosome; late endosome; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

PIK3C3 links:

PIK3C3 (HGNC:):

PIK3C3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.752

BS2

High AC in GnomAdExome4 at 136 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3C3	NM_002647.4 linkuse as main transcript	c.19T>G	p.Phe7Val	missense_variant	1/25	ENST00000262039.9	NP_002638.2	Q8NEB9
PIK3C3	NM_001308020.2 linkuse as main transcript	c.19T>G	p.Phe7Val	missense_variant	1/24		NP_001294949.1	A8MYT4B4DPV9
PIK3C3	XM_047437549.1 linkuse as main transcript	c.19T>G	p.Phe7Val	missense_variant	1/22		XP_047293505.1
PIK3C3	XM_047437551.1 linkuse as main transcript	c.19T>G	p.Phe7Val	missense_variant	1/14		XP_047293507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PIK3C3	ENST00000262039.9 linkuse as main transcript	c.19T>G	p.Phe7Val	missense_variant	1/25	1	NM_002647.4	ENSP00000262039.3	Q8NEB9
PIK3C3	ENST00000586545.5 linkuse as main transcript	c.19T>G	p.Phe7Val	missense_variant	1/4	1		ENSP00000465621.1	K7EKH3
PIK3C3	ENST00000398870.7 linkuse as main transcript	c.19T>G	p.Phe7Val	missense_variant	1/24	2		ENSP00000381845.2	A8MYT4
PIK3C3	ENST00000590220.1 linkuse as main transcript	n.49T>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250566

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000931

AC:

136

AN:

1461178

Hom.:

Cov.:

AF XY:

0.0000867

AC XY:

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000122

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000302

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2024

The c.19T>G (p.F7V) alteration is located in exon 1 (coding exon 1) of the PIK3C3 gene. This alteration results from a T to G substitution at nucleotide position 19, causing the phenylalanine (F) at amino acid position 7 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.30

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Pathogenic

0.82

D;.;T;.

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Pathogenic

0.36

MetaRNN

Pathogenic

0.75

D;D;D;D

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.2

M;.;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-4.8

D;.;D;.

REVEL

Uncertain

0.59

Sift

Benign

0.072

T;.;T;.

Sift4G

Uncertain

0.059

T;.;T;D

Polyphen

0.075

B;.;B;.

Vest4

0.68

MutPred

0.61

Gain of ubiquitination at K6 (P = 0.1686);Gain of ubiquitination at K6 (P = 0.1686);Gain of ubiquitination at K6 (P = 0.1686);Gain of ubiquitination at K6 (P = 0.1686);

MVP

0.87

MPC

0.71

ClinPred

0.88

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.73

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over